An investigation will be made of the effect of snake venom proteinases on human plasma proteinase inhibitors. Two proteinases have been purified from Crotalus adamanteus venom and shown to enzymatically inactivate human alpha 1 proteinase inhibitor by limited proteolysis. A single bond in the amino terminal region of the molecule is cleaved by the proteinases. Crotalid, Viperid and Colubrid venoms have been shown to inactivate all the detectable trypsin and chymotrypsin inhibitory activity in human serum. Several Crotalid and Viperid venoms and partially purified C. adamanteus proteinases also digest human plasma alpha 1 antichymotrypsin. Proteinases from these venoms also interact with human alpha 2 macroglobulin. Studies are in progress to determine the mechanism of action of the pure venom proteinases on human alpha 1 antichymotrypsin, alpha 2 macroglobulin and antithrombin III.